08 April 2009

Interview w/Professor Blackburn

Prof. Elizabeth H. Blackburn (physiology, biology, UC Berkeley) researches the ends of eukaryotic chromosomesWT, or telomeresW. I became aware of her entirely as a result of reading the interview in Frontline of India.

Blackburn's research became interesting to the broader public as a result of discoveries that there was a very strong link between telomeres and health conditions associated with aging.

Yes. We are looking at that. There are these successfully treated AIDS patients who have been on high activity antiretroviral therapy [HAART] for some years. Their lives have been saved, and they have been kept going for years on these drugs. The virus is kept [at a] very low [level] although it is never completely contained. And do you know what’s happening? It’s sort of an epidemic. These [successfully treated HAART] individuals are now developing diseases that look like the diseases of the aged. For their age group, these people are getting more cardiovascular diseases, more dementia, more osteoarthritis, more renal disease and a whole spectrum of diseases that are [making them] look as if they are really old.

Telomeres are regulated and restored through an unusual combination protein-enzyme known (naturally) as "telomerase." As cells divide, the telomeres at the end of each chromosome are subdivided until they are either restored or depleted. If the telomere is depleted, the cell cannot subdivide and therefore dies. In some cases, the body supplies cells with telomerase to enable continuing subdivision and growth. In other cases, cells "develop" the ability to supply their own telomerase; their growth ceases to be regulated by the body, and they can become cancerous.

Prof. Blackburn and her assistant, Carol Greider, discovered telomerase in the 1970's. The implications of telomerase in the lives of cells was extremely far-reaching: it affected research into cancer, AIDS, aging, and organ regeneration.

The interview is pretty basic, and mostly geared to readers like myself who have never heard of telomerase. However, it veers towards speculation towards the end:

FLO: Though we know that diseases are caused by a whole lot of factors, do you see a kind of paradigm developing that would ultimately, perhaps in the distant future, lead to a unidirectional telomerase-based approach for attacking disease?

EHB: You know part of me wants to say yes. That would be terrific, but you risk hubris when you say something like that because you are then immediately proved wrong. But, as I said, because so much evidence has come in a consistent fashion, this seems like a pretty good attack on the problem. We see [that] these environmental factors like chronic stress are obviously acting on telomerase and telomere lengths through the immune system. We also see [that] when people are dealing with their stress well, it is correlating with having higher [levels of] telomerase and better telomere lengths. We put two and two together and say what if people could be helped to deal with their stresses.

Now you can’t change life. You can’t change the fact that somebody had a chronically ill childhood or the father has dementia. But, maybe, you can give people these tools, or things they can do that will help them cope. Would that modulate their telomerase up? I love it because it is very, very cheap.

I can imagine this would lead to a massive boom in the biochip industry as therapy becomes dominated by direct polymerase sampling and chain reactions. A web search turned up this recent patent for a biochip that directly captures and analyzes circulating tumor cells (CTC).

Sources & Additional Reading:SuperscriptW links to relevant Wikipedia article; superscriptC to Cells Alive article; superscriptT to Library/Thinkquest article. Errors in the summary below are my fault, and not the fault of the linked authors.

The reference to HAART involves some explanation: HIV, the virus that causes AIDS, is known as a retrovirusWC it attacks the actual DNA of the patient via the enzyme for DNA replication (i.e., RNA), and thereby integrates itself into the patient's DNA. As a consequence, antiretroviral therapy (ART) mainly consists of chemical inhibitors. Usually ART is administered with several inhibitors (sometimes referred to as a "cocktail"), in which case it is known as "high activity" ART, or HAART. See "Recommended HIV Treatment Regimens" and "Approved Medications to Treat HIV Infection" , US Department of Health and Human Services (Dec 2008).

Put another way, therapies for AIDS target the process of cell reproduction at the polymerase level—at the point in which DNA strands are replicated through interaction with the enzyme RNAW. This naturally has deleterious side-effects, since some desirable polymerase activity is also suppressed. The overall effect is similar to regular aging: as organisms get older, their body fails to reproduce moribund cells.

04 April 2009

Future Combat Systems

Costliest weapons program ever?

Click for larger imageM1203 NLOS-C 155mm howitzer

One major source of technological innovation is, naturally, warfare and international competition. It seems self-evident that much of modern weapon systems development is guided not so much by current conflicts (with insurgents in Iraq and Afghanistan, who mainly focus on "soft targets") but a tacit competition with other major industrialized powers. Hence, the ongoing race to develop more "competitive" jet fighters, naval weapons systems, and so on.

Weapons systems also constitute an obvious form of technology that is not morally neutral. For example, while the use of the nuclear bomb against Japan may have helped the Allies hasten the defeat of a dangerous regime, the ramifications of use were a disaster for democracy. The FCS represents a weapons program (now in transition) with the seemingly uncontroversial objective of modernizing existing weapons systems in a comprehensive way. Land-based weapons systems are intended to mesh with enhancements of air-based and sea-based systems, and all are to exploit the latest developments in space-based telemetry.

The core of the FCS program has been the non-line-of-sight (NLOS) cannon, mortar, and launch system. Three other systems are robotic: sensors, unmanned vehicles, and unmanned aircraft. The NLOS systems are to be installed on some of the eight manned ground vehicles (MGV) in the program. The launch system (NLOS-LS) can be described as a "snap-on Katyusha": a box of 15 small missiles and a control system, capable of being bolted onto truck beds or sea vessels.

Click for larger imageNLOS-LM Netfires PAM

Interestingly, the FCS clinically categorizes Army weapons systems by the range, caliber, and precision of their firepower. The platforms for the combat MGV's is standardized, suggesting that the old days of tank warfare are understand to have passed: in the past, main battle tanks (MBT's) were designed as massive rolling bunkers with as large a gun as could be accommodated with the weight of the armor. The Mounted Combat System (MCS-XM1202) is intended to succeed today's MBT's, but the basic "vehicle" is identical to that used by the XM1203 NLOS-C (which is simply a self-propelled artillery piece) and the XM1204 mortar.

The most decisive component seems to be the NLOS-LS "Netfires" Precision Attack Munitions (PAM). What makes this so important is that it is supposedly capable of destroying nearly any form of mechanized tank. A box could be parked scores of kilometers away from the theater, and a remotely-piloted or "unmanned aerial vehicle" (UAV) could loiter over the battlefield. The UAV could target an endless number of enemy objects and remotely guide missiles to them. Currently, the unpiloted drones used in Afghanistan/NWFP of Pakistan have carried their missiles, limiting their lethality and range. The NLOS-LM is regarded as so effective, that FCS was designed with the assumption that any adversary would be unable to use tank busting weapons against its MGV's.

But of course the MGV's represent a revenant of the mechanized Army, much the way the Strategic Air Command (SAC) fought successfully to maintain a fleet of airplanes as nuclear weapon delivery systems, long after they'd been rendered obsolete by ICBM's and SLBM's. There's little compelling reason to spend scores of billions on totally new mortars, self-propelled artillery, and "neo-tanks" (XM1202's) when incremental improvements will suffice, and unsurprisingly the MGV's are the part of the program that the White House wants to delay.

All this time, Predator drones have fired many missiles in Afghanistan; the drone attacks have been notoriously ineffective as a strategy, since the killings seem to have stimulated support for the Taliban faster than they've eliminated significant Taliban officials. Since 2006 there have reportedly been 60 drone attacks with a death toll of >500.1 In early 2009 a large number of drone attacks were launched against targets in Pakistan, understandably provoking outrage; the attacks violated Pakistani sovereignty, yet provided nothing whatever to the Pakistanis in exchange (unlike, say, US support to regimes facing armed insurgencies).

Another component of the FCS is the armed robotic vehicles (ARV's), which seem to remain a small component. Very little recent literature on the ARV program is available online, but the system seems to be pursuing unpiloted, "intelligent" robots. These would be self-guided combatants, like the fire-and-forget missiles. Even if the fulfillment of this goal by the ARV program remains incomplete, it's very disturbing.

Of the programs I've described, one seems to be progressing successfully: the NLOS-LM Netfires PAM. The contractor for this program is Netfires LLC, a joint venture of Raytheon and Lockheed Martin. The entire rest of the program is under EADS, a massive British contractor descended from British Aerospace (and former Airbus partner).Notes

Non-line-of-sight (NLOS) refers to one of many important features of the NLOS-C, NLOS-M, and NLOS-LS. Both permit the user to target objects that are over the horizon, behind a mountain, or otherwise invisible. In the case of the launch system, NLOS includes the ability of a missile to "loiter" in the sky while it seeks a target, and then aim itself at the newly acquired target. This is also called "fire-and-forget."

NLOS is also used to refer to wireless technology (IEEE 802.16, or WiMax) that permits connections to a base station that is likewise over the horizon.